| Popis: |
Epithelial ovarian cancer remains highly lethal regardless of geography, technology, or finances. High-grade serous cancer (HGSC) is associated with p53 loss, defective apoptotic signaling, genomic instability, defective DNA repair, peritoneal dissemination, angiogenic signaling, and drug resistance. Primary therapy with cytoreductive surgery and platinum-based chemotherapy has changed minimally over 30 y, with improved PFS and OS, but without any impact on mortality. Ambitious strategies to restore defective apoptotic signaling (p53), overcome drug resistance, modulate the immune response, and target tumor stem-like populations are needed. Increased prevalence of genomic screening will facilitate decisions regarding lifestyle modifications and risk-reduction surgery. Functional imaging and molecular probes will improve high-risk detection and accuracy of staging, including intra-operative probes to localize microscopic disease. Adjuvant therapy will be reserved for women with HGSC and pre-defined molecular-biologic risk factors. Vaccines with immune response modulation will eventually replace chemotherapy for early-stage disease. Patients with high-volume disease will undergo risk-profiling for neoadjuvant chemotherapy and interval cytoreduction. Intraperitoneal therapy will be offset by targeted agents. Important generic drugs in recurrent disease will receive extended patent protection to assure adequate supply of high-quality reagents. Sequential tumor specimens will be routinely evaluated for clonal evolution and pathway activation. A research foundation will be established through pharmaceutical collaboration with government agencies, eliminating barriers to international research. New agents/combinations will be evaluated in small randomized trials to select promising regimens. Molecular profiles will be standardized and shared to facilitate design and analysis of clinical trials. The accelerated pace of discovery has not yet translated into a reduction in mortality for patients with HGSC, although a number of promising interventions are under development. The next decade will witness a concerted effort to apply technology to address high-priority clinical, scientific, regulatory, information-based, and financial goals. Disclosure: M.A. Bookman: Chair Ovarian Comm NRG-GOG; member independent data monitoring committees industry-sponsored; participant ad-hoc advisory boards clinical trial development investigational agents. Support for attendance. No financial holdings. |
